Significant advances have been made concerning the characterization of interferon (IFN): the major species have been classified, genes coding for IFN have been identified, and a number of monoclonal antibodies have been developed. However, before the most effective therapeutic applications of IFN can be designed, more information concerning IFN activity in vivo is required. These studies can most effectively be performed in animals. Based on the need for in vivo experimentation with IFN and the availability of monoclonal antibodies to murine IFN, the proposed study will: 1) isolate large quantities of pure species of natural induced murine IFN-Alpha and IFN-Beta using monoclonal antibodies; 2) determine the antigenic and functional relationships of these IFN species in vitro; 3) establish and compare the in vivo effectiveness of pure murine IFN subspecies to regulate immune responsiveness and alter tumor growth; and 4) define the mechanism of these IFN-mediated effects. Particular emphasis will be placed on investigation of the ability of murine IFN to inhibit lymphocyte recirculation since this effect may be pivotal in determining whether IFN will inhibit or enhance immune responses. The mechanism of the increase in circulating natural killer cell activity in the presence of a decrease in the total number of circulating cells will also be established. These studies will provide information concerning the mechanism of IFN activity in vivo that is essential for realization of the clinical potential of IFN immunotherapy.